Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Cystic fibrosis gene mutations missing from some cases

16.10.2002


A new study from Johns Hopkins finds that some patients diagnosed with cystic fibrosis (CF) lack any of the more than 1,000 reported disease-causing mutations in the only known CF gene. Scheduled for presentation Oct. 18 at the annual meeting of the American Society for Human Genetics in Baltimore, the findings also recently appeared in the New England Journal of Medicine.



The discovery may mean that another gene, as yet unidentified, is to blame for these cases, or perhaps these patients really have another, unknown disease, despite the similarity of symptoms, the researchers suggest.

Loss of the function of a protein called CFTR was identified more than a decade ago as the cause of CF, a life-shortening disease characterized by frequent, severe lung infections. In less severe cases, known as "non-classic" CF, patients retain some working CFTR, but not at normal levels. Over the years, scientists have linked these conditions to more than 1,000 changes in the gene for CFTR.


"Our findings should lead to a discussion about what is, and is not, non-classic cystic fibrosis," says Garry Cutting, M.D., director of the DNA Diagnostic Lab at the McKusick-Nathans Institute of Genetic Medicine at Hopkins. "Hopefully, extensive clinical evaluation of patients without identifiable changes in the gene for CFTR will improve diagnosis and treatment of cystic fibrosis and cystic fibrosis-like conditions."

In the new study, of 74 patients diagnosed with non-classic CF and referred to the Cystic Fibrosis Foundation Genotyping Center at Hopkins, detailed genetic analysis showed that 29 had mutations in both copies of the CFTR gene, 15 had only a single mutation and 30 had no detectable changes in their CFTR genes. (One copy is inherited from each parent.) Cutting says other researchers now report the same observation.

"These patients were referred by physicians experienced with cystic fibrosis, and we expected to find a causative mutation in each copy of each patient’s CFTR gene," says Cutting, who also heads the genotyping center. "While it’s possible we could have missed some mutations, we believe they just weren’t there to be found in these patients."

The researchers looked for changes in the CFTR gene in areas that carry instructions for the CFTR protein and those that control the expression of the gene. It might be possible that changes to the CFTR protein, unrelated to the sequence of its gene (so-called "epigenetics"), are at the root of these patients’ conditions.

To cause disease, any changes must reduce or alter how the CFTR protein works. In classic CF, there’s no working CFTR protein, and a thick mucous forms that traps bacteria in the airways, causing infections. In the non-classic version, the theory held that some working CFTR protein remained to transport charged atoms and water into and out of cells, while symptoms run the gamut from mild to severe.

First surprised that many patients lacked any mutations in their CFTR genes, the scientists were surprised again when symptoms were the same for these patients and those with one or two CFTR mutations. For each measurement, including the standard test for CFTR function that measures the amount of salt in sweat, each group looked like the others.

"Once we saw that we had a large number of patients without changes in CFTR, we thought we’d be able to demonstrate that they had a different condition," says Cutting. "But we couldn’t."

The Cystic Fibrosis Foundation Genotyping Center at Johns Hopkins was launched in 1998 to look for genetic changes responsible for cases of non-classic cystic fibrosis that couldn’t be explained by the most common known mutations.

The Hopkins researchers are putting together a detailed account of each patient’s symptoms, biochemical and electrophysiological measurements, genetic status, and possible non-genetic contributors to find subtle differences between the groups that will allow physicians to distinguish between conditions linked to CFTR mutations and those that aren’t.

Joanna Downer | EurekAlert!
Further information:
http://www.ashg.org
http://www.nejm.org

More articles from Health and Medicine:

nachricht Biofilm discovery suggests new way to prevent dangerous infections
23.05.2017 | University of Texas at Austin

nachricht Another reason to exercise: Burning bone fat -- a key to better bone health
19.05.2017 | University of North Carolina Health Care

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Can the immune system be boosted against Staphylococcus aureus by delivery of messenger RNA?

Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.

Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

How herpesviruses win the footrace against the immune system

26.05.2017 | Life Sciences

Water forms 'spine of hydration' around DNA, group finds

26.05.2017 | Life Sciences

First Juno science results supported by University of Leicester's Jupiter 'forecast'

26.05.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>